Catastrophic antiphospholipid syndrome: A prototype of autoimmune thromboinflammation

Antiphospholipid syndrome (APS) is defined as “an autoimmune thromboinflammatory disease characterized by an increased risk of thrombosis localized in the venous and arterial vascular beds, thrombotic damage to microvessels, placental insufficiency, cytopenia, skin and heart valves lesions, nephropathy, pulmonary hemorrhages, etc.”. Long with clinical symptoms, the cardinal hallmark of APS is antibodies to phospholipids and phospholipid-binding proteins and including lupus anticoagulant, antibodies to cardiolipin, and antibodies to β2-glycoprotein I, highlighting the leading autoimmune mechanism of this pathogenesis. APS is considered an important problem in modern medicine, located at the intersection of rheumatology and hematology. A distinctive feature of APS is heterogeneity, which manifests itself both at the clinical (phenotypes, course variants) and pathogenetic levels (molecular endotypes). Particular attention is drawn to the potentially lethal form of APS, manifested by the fulminant development of multiorgan thrombosis, which was first identified by Ronald A. Asherson in 1992 as the “catastrophic” form of APS (CAPS). Currently, approaches to personalized therapy of APS using artificial intelligence and, on this basis, the implementation of the concept of “treat-to-target” aimed at achieving remission, which in APS should be considered as the absence of recurrent thrombosis, are being actively discussed. The implementation of this strategy in autoimmune rheumatic diseases has largely become possible thanks to the development and introduction of a wide range of biologics, which are monoclonal antibodies or hybrid molecules that selectively modulate key mechanisms of immunopathogenesis. The clinical forms of CAPS and the pathogenetic mechanisms of APS are considered, and on this basis, new possibilities for the treatment of CAPS using anti-B-cell therapy, complement inhibitors (eculizumab), prospects for the prevention of thrombosis associated with comorbid cardiometabolic pathology.